Receptor structural classification

Cytokines can be grouped into families based upon their shuctural homology or structural homology of their receptors. Below, is an effort to group cytokines and their families based on the structural homology of their receptors. This classification helps provide a foundation for thinking about these factors and their role in the brain. 

Different kinds of opioid receptors have been distinguished in mammals. This classification, which is based on pharmacological behaviour, may be accepted (but with reserve) until the receptor structures are better known. There may, for example, be grouping, or conformational equilibria of a smaller number. of receptors l ord et al, 1977 Iwamotoand Martin, 1981). 

This structure encoding method has been applied both for the classification of a data set comprising 31 corticosteroids, for which affinity data were available in the literature, binding to the corticosteroid-binding globulin (CBG) receptor, and for the simulation of infrared spectra [28, 29). 

Barnard EA, Skolnick P, Olsen RW et al (1998) International Union of Pharmacology. XV. Subtypes of y-aminobutyric acidA receptors classification on the basis of subunit structure and receptor function. Pharmacol Rev 50 291-313... 

Measurement of dissociation equilibrium constants, which is of particular value in receptor classification and in the study of structure/activity relationships, where the effects of changes in chemical structure on affinity (and efficacy) are explored. 

It was noted, however, that a subset of responses known to be triggered by histamine failed to be blocked by the classical antihistaminic drugs. This, as well as further sophisticated pharmacological work, led to the classification of histamine receptors as and Hg. To simplify grossly, the receptor controls the responses familiar to every hayfever sufferer these effects can be alleviated readily by classicial antihistamines. The latter interestingly bear little or no structural similarity to histamine... 

FIGURE 11-3 Structure of compounds important to the classification of receptor subtypes at cholinergic synapses. Compounds are subdivided as nicotinic (N) and muscarinic (Ad). The compounds interacting with nicotinic receptors are subdivided further according to whether they are neuromuscular (N,) or ganglionic (N2). Compounds with muscarinic subtype selectivity (M M2, M3, M4) are also noted. 

Thus, cholinergic receptor classification can be considered in terms of three stages of development. Initially, Dale [2] distinguished nicotinic and muscarinic receptor subtypes with crude alkaloids. Then, chemical synthesis and structure-activity relationships clearly revealed that nicotinic and muscarinic receptors were heterogeneous, but chemical selectivity could not come close to uncovering the true diversity of receptor subtypes. Lastly, analysis of subtypes came from molecular cloning, making possible the classification of receptors on the basis of primary structure (Fig. 11-2). 

Two very similar molecules are two different physical objects [40], Hence, chemical/ structural comparison of similarity is a subtle and relative concept that acquires significance in a well-defined reference physical context. In other words, it is necessary to define in what respect and to what extent two different molecules are similar. Molecular series of specific and selective ligands interacting, in vitro and in equilibrium conditions, with a specific receptor constitute a sophisticated example of chemical similarity-diversity classification. This classification is based on the experimental binding affinity (AG°) values that quantify a particular molecular recognition phenomenon, which is, essentially, a noncovalent process [41]. This implies,... 

---